The objective of this Component is to determine if epidural stimulation of the spinal cord can be used for intervention and rehabilitation of posture and locomotion following spinal cord injury (SCI) in the cat. We have determined that epidural stimulation of the lumbar enlargement (LE) using low frequencies (1-5 Hz) will induce hindlimb stepping soon after complete spinal cord transection at thoracic levels. Higher frequency stimulation (>10Hz) was found to lead to rigidity (antagonist cocontraction) of the hindlimbs (i.e. standing). The proposed studies will determine if epidural LE stimulation can be used to induce locomotion or standing for prolonged periods (weeks or months) following SCI. The ability of pharmacological agents to reduce the electrical threshold, augment the electrical stimulation-induced effects or reinstate locomotion or standing if electrical stimulation is no longer effective, all will be tested. A treadmill training and standing training regimen will be instituted. Since the use of prostheses and/or rehabilitative interventions in the SCI patient may be delayed, we will test the effects of 30 and 90 day waiting periods on the efficacy of epidural LE stimulation-induced locomotion or standing. Finally, we will test the possible additional salutary effects which fetal spinal cord implants made into the injury site will have on electrically- and/or chemically-induced locomotion and standing. We will analyze the changes in the locomotor step cycle and electromyographic measures of standing induced by epidural electrical stimulation and/or pharmacological therapy. In terminal experiments, changes in spinal cord circuitry will be measured using the H-reflex. The force and fatigability of relevant hindlimb muscles in one hindlimb will be tested in order to determine the possible salutary effects of these interventions on muscle function. Muscles in the other hindlimb will be analyzed immunocytochemically for myofiber size changes and the expression of relevant myosin heavy chain isoforms. These results will reveal specific fiber size and type changes effected by the various palliative strategies described. In addition, immunocytochemical labeling of specific transmitter types will be used to detect changes induced by SCI and possible alterations of those changes induced by the interventions described. This comprehensive study will test a promising prosthetic device for its potential to be used exclusively or in combination with pharmacotherapeutic intervention, neurotransplantation and/or training regimens. We will test its ability to reduce the deficits and, perhaps, improve postural, locomotion, reflex and muscular function after SCI.